Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial

Objective Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants.Design EP infants (gestational age (GA) <28 weeks)...

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Main Authors: Gayatri Athalye-Jape, Karen Simmer, Sanjay Patole, Liwei Chen, Shripada Rao, Lakshmi Chandrasekaran, Dorota Doherty, Meera Esvaran, Elizabeth Nathan, Anthony Keil, Chooi Kok, Stephan Schuster, Patricia Conway
Format: Article
Language:English
Published: BMJ Publishing Group 2022-09-01
Series:BMJ Open Gastroenterology
Online Access:https://bmjopengastro.bmj.com/content/9/1/e000811.full
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author Gayatri Athalye-Jape
Karen Simmer
Sanjay Patole
Liwei Chen
Shripada Rao
Lakshmi Chandrasekaran
Dorota Doherty
Meera Esvaran
Elizabeth Nathan
Anthony Keil
Chooi Kok
Stephan Schuster
Patricia Conway
author_facet Gayatri Athalye-Jape
Karen Simmer
Sanjay Patole
Liwei Chen
Shripada Rao
Lakshmi Chandrasekaran
Dorota Doherty
Meera Esvaran
Elizabeth Nathan
Anthony Keil
Chooi Kok
Stephan Schuster
Patricia Conway
author_sort Gayatri Athalye-Jape
collection DOAJ
description Objective Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants.Design EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks’ corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing.Results 173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8–16) vs 10 (IQR 8–16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF.Conclusion TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies.Trial registration number ACTRN 12615000940572.
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spelling doaj-art-e12b59ed0e5241f1a163f52ceeb163d92025-08-20T03:21:24ZengBMJ Publishing GroupBMJ Open Gastroenterology2054-47742022-09-019110.1136/bmjgast-2021-000811Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trialGayatri Athalye-Jape0Karen Simmer1Sanjay Patole2Liwei Chen3Shripada Rao4Lakshmi Chandrasekaran5Dorota Doherty6Meera Esvaran7Elizabeth Nathan8Anthony Keil9Chooi Kok10Stephan Schuster11Patricia Conway122 University of Western Australia, Perth, Western Australia, AustraliaDepartment of Neonatology, Perth Children’s Hospital, Perth, Western Australia, Australia1 Neonatal Paediatrics, KEM Hospital for Women, Perth, Western Australia, AustraliaGenomics and Bioinformatics, Nanyang Technological University, SingaporeMedical School, The University of Western Australia, Perth, Western Australia, Australia8 Nanyang Technological University, SingaporeBiostatistics, Women and Infants Research Foundation Western Australia, Subiaco, Western Australia, Australia3 University of New South Wales, Sydney, New South Wales, AustraliaBiostatistics, Women and Infants Research Foundation Western Australia, Subiaco, Western Australia, AustraliaMicrobiology, PathWest Laboratory Medicine Western Australia, Nedlands, Western Australia, Australia1 Neonatal Directorate, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia1University of Pennsylvania, Philadelphia, PA, USA9 Centre for Marine Bio-Innovation, University of Newsouth Wales, Sydney, New South Wales, AustraliaObjective Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants.Design EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks’ corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing.Results 173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8–16) vs 10 (IQR 8–16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF.Conclusion TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies.Trial registration number ACTRN 12615000940572.https://bmjopengastro.bmj.com/content/9/1/e000811.full
spellingShingle Gayatri Athalye-Jape
Karen Simmer
Sanjay Patole
Liwei Chen
Shripada Rao
Lakshmi Chandrasekaran
Dorota Doherty
Meera Esvaran
Elizabeth Nathan
Anthony Keil
Chooi Kok
Stephan Schuster
Patricia Conway
Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
BMJ Open Gastroenterology
title Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
title_full Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
title_fullStr Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
title_full_unstemmed Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
title_short Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial
title_sort effect of single versus multistrain probiotic in extremely preterm infants a randomised trial
url https://bmjopengastro.bmj.com/content/9/1/e000811.full
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